Leveraging Public Health Research to Inform State Legislative Policy that Promotes Health for Children and Families.

Purpose Engagement in policy is an essential public health service, with state legislatures serving as important arenas for activity on issues affecting children and families. However, a gap in communication often exists between policymakers and public health researchers who have the research knowledge to inform policy issues. We describe one tool for researchers to better leverage public health research to inform state legislative policymaking on issues of relevance to children and families. Description The Oregon Family Impact Seminar (OFIS), adapted from the Policy Institute for Family Impact Seminars, applies a systematic process to bring a synthesis of research findings on public health issues to state legislators using a six-step process: (1) identify candidate topics, (2) recruit legislative champions, (3) select the topic, (4) identify and prepare speakers, (5) host the presentations, and (6) develop and disseminate a research brief as a follow-up contact. Assessment Use of this model in Oregon has produced policy impact; for example, the 2015 presentation, "Two-Generation Approaches to Reduce Poverty," prompted ongoing dialogue culminating in a new statute to increase Earned Income Tax Credit for parents with young children. This approach also has strengthened relationships among researchers and legislators, which serves to streamline the OFIS process. Conclusion This model is an effective vehicle for leveraging public health research findings to inform state-level policy. This model also serves to connect researchers with opportunities to engage with policymakers to address significant public health problems, particularly those addressing social, economic, and environmental determinants of health for children and families.

Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation.

OBJECTIVE: The NADPH oxidase isoforms Nox2 and Nox4 are coexpressed in many cell types and are implicated in agonist-stimulated redox-sensitive signal transduction. We compared the involvement of Nox2 versus Nox4 in redox-sensitive protein kinase activation after agonist stimulation. METHODS AND RESULTS: We transfected HEK293 cells with Nox2 or Nox4 and compared ROS production and activation of mitogen activated protein kinases (MAPKs), Akt, and GSK3beta after acute agonist stimulation. Nox4 overexpression substantially increased basal ROS generation whereas ROS generation in response to angiotensin II and tumor necrosis factor (TNF)alpha was enhanced in Nox2-overexpressing cells. Nox4 overexpression induced basal activation of ERK1/2 and JNK whereas Nox2-transfected cells showed a modest increase in p38MAPK activation. After angiotensin II or TNFalpha treatment, JNK activation was augmented in Nox2 but not Nox4-transfected cells, whereas insulin augmented phosphorylation of p38MAPK, Akt, and GSK3beta specifically in Nox4-overexpressing cells and JNK specifically in Nox2-overexpressing cells. CONCLUSIONS: These data indicate that Nox2 and Nox4 exhibit distinctive patterns of acute activation by angiotensin II, TNFalpha, and insulin and regulate the activation of distinct protein kinases.

FXYD1 phosphorylation in vitro and in adult rat cardiac myocytes: threonine 69 is a novel substrate for protein kinase C.

FXYD1 (phospholemman), the primary sarcolemmal kinase substrate in the heart, is a regulator of the cardiac sodium pump. We investigated phosphorylation of FXYD1 peptides by purified kinases using HPLC, mass spectrometry, and Edman sequencing, and FXYD1 phosphorylation in cultured adult rat ventricular myocytes treated with PKA and PKC agonists by phosphospecific immunoblotting. PKA phosphorylates serines 63 and 68 (S63 and S68) and PKC phosphorylates S63, S68, and a new site, threonine 69 (T69). In unstimulated myocytes, FXYD1 is approximately 30% phosphorylated at S63 and S68, but barely phosphorylated at T69. S63 and S68 are rapidly dephosphorylated following acute inhibition of PKC in unstimulated cells. Receptor-mediated PKC activation causes sustained phosphorylation of S63 and S68, but transient phosphorylation of T69. To characterize the effect of T69 phosphorylation on sodium pump function, we measured pump currents using whole cell voltage clamping of cultured adult rat ventricular myocytes with 50 mM sodium in the patch pipette. Activation of PKA or PKC increased pump currents (from 2.1 +/- 0.2 pA/pF in unstimulated cells to 2.9 +/- 0.1 pA/pF for PKA and 3.4 +/- 0.2 pA/pF for PKC). Following kinase activation, phosphorylated FXYD1 was coimmunoprecipitated with sodium pump alpha(1)-subunit. We conclude that T69 is a previously undescribed phosphorylation site in FXYD1. Acute T69 phosphorylation elicits stimulation of the sodium pump additional to that induced by S63 and S68 phosphorylation.

Enhanced expression of the mannose receptor by endothelial cells of the liver and spleen microvascular beds in the macrophage-deficient PU.1 null mouse.

Mice null for the haematopoietic lineage-specific transcription factor PU.1 lack mature Mphi and are compromised in their ability to clear cellular debris from the blood circulation. We investigated the possibility that non-professional phagocytes may partially compensate for the lack of Mphi in clearance functions. In the absence of Kupffer cells (resident liver Mphi) in the PU.1 null mice, electron microscopy revealed ingested debris in sinusoidal endothelial cells and hepatocytes although debris was also seen free in blood vessels. To investigate whether an increased clearance function of non-professional phagocytes might be linked to expression of Mphi-associated phagocytic and pinocytic receptors by other cells in PU.1 null mouse, we examined expression of several candidate proteins by immunocytochemistry and Western blotting. We found mannose receptor (MR) comparably expressed in PU.1 null and PU.1+ mice liver and spleen whereas class A scavenger receptor was substantially reduced and complement receptor 3 was absent in PU.1 null animals. By morphometric analysis, liver and spleen sinusoidal endothelial cells were seen to express significantly more MR in the PU.1 null mouse. This study provides the first evidence of apparently compensatory alterations in the microvasculature of the Mphi-deficient PU.1 null mouse.